Organ transplantation saves thousands of lives every year and is the treatment of choice for end stage organ failure. Despite awareness of importance of transplantation, a gulf remains between the supply and need for life-saving organs. This is predicted to worsen over the next decade, making this disparity a key challenge facing the transplant community today. Due to this shortage, nowadays older and higher risk donors are accepted. However, uncertainty as regards transplantability often results in decline and sometimes discard of scarce organs. Between April 2015 and March 2016, 479 patients died waiting for a lifesaving transplant. A further 3,452 patients were temporarily suspended from the waiting list because they were unfit for transplant. The Quality in Organ Donation (QUOD) Biobank was established in 2012. This unique resource combines collection of detailed clinical information from virtually all organ donors in the UK with blood and urine samples taken around the time of donation and carefully collected small biopsies from a range of organs stored within a central 'bank'. This has been invaluable in research focused on understanding how stress associated with becoming an organ donor around the time of death affects control of important whole body systems such as blood pressure and glucose levels in addition to impact on specific organs. This has already enabled otherwise impossible research focused on better selection and optimisation of organs enhancing successful transplantation. The pancreas, heart and lungs work in concert to maintain glucose levels, blood pressure and effective oxygenation throughout life. The extreme stress around the time of death has a major impact on these control systems. Despite a huge unmet clinical need, 'conversion' of these organs into successful transplants is much lower than in kidney transplantation. Impairment and failure of these organs is also central to many of the most common and challenging chronic diseases, including diabetes, heart failure; and lung disease. We propose to expand QUOD to include samples from pancreas, heart and lungs and will work closely with MRC Units to ensure provision to the research community of highest quality state-of-the-art clinical pathology and molecular techniques as well as single cell analysis platforms, in addition to facilities expert in processing organs to retrieve live functioning cells. This will allow us to create detailed atlases and a data library representing the range of normal, acutely stressed and chronically diseased tissues from these organs that can be seldom accessed in life which has severely limited true understanding of mechanisms driving damage and failure. This type of resource linked to such high quality clinical information and a library of new markers associated with these processes and easily monitored from blood samples does not currently exist. The QUOD remit and proposed expansion will be made accessible to the widest possible scientific and clinical community. It will enable new understanding of causes of organ stress, facilitating new treatments to maximise transplant success and ultimately help to prevent / reverse chronic diseases without need for transplantation. In type 1 and 2 diabetes it is becoming clear that insulin-producing cells are not completely destroyed, offering exciting new possibilities for reactivating function which may ultimately lead to a cure for this burdensome and dangerous disease. Deeper understanding of mechanisms underlying heart pump failure will facilitate increased numbers of heart transplants but also new treatments for all with chronic heart failure targeting specific processes damaging the muscle. Elucidation of the causes of scarring lung disease will be accelerated through this resource. Moreover, previously impossible parallel research exploring pathological interplay between pancreas, heart and lungs with already collected data on liver and kidney will be enabled.

The issue: There are currently more people over the age of 60 than ever before. The Office of National Statistics have projected that the number of people age 60 years and over will increase by 50% in the next 25 years. These demographic changes are important because people generally become less physically active as they grow older. This can be detrimental to their health and well-being and has subsequent health and social care costs. Researchers have been investigating the relationship between physical activity and health for a long time. Consequently, much is known about which diseases can be prevented through physical activity, and how much and how often activity should be undertaken. This information is useful, but it does not negate the fact that there are still lots of older people who are inactive. Recently, leading scientists have said that if we are to encourage people to integrate health behaviours like physical activity into their everyday life, conducting research to reconfirm that physical activity is beneficial is not enough. Instead, they say that we need to know more about the different environments, which can enable or deter physical activity in older age and shape how it is experienced. This includes people's physical environments (e.g. their access and proximity to woodlands, parks etc.) and also their social and cultural environments (e.g. the impact of their ethnicity, gender, interaction with healthcare etc.). Social scientists are well qualified to investigate issues like these. Our response: Our seminar series will bring together academics from different subject areas (e.g. sociology, psychology, geography, sport and health sciences), policy makers, health and social care practitioners, physical activity and sport providers, and those working within the voluntary and statutory sectors. Each seminar will focus on a specific issue relevant to the physical, social and cultural environments that can impact upon physical activity (PA) in older age. Specifically; (i)competitive sport in later life, (ii)physical activity during lifecourse transitions, (iii)how gender impacts upon physical activity involvement - and vice versa, (iv)experiences of physical activity amongst hard to reach groups (e.g. ethnic minorities), (v)community based initiatives to promote physical activity, (vi)E-health, (vii)PA in the outdoor natural environment, (viii)the process of using research to inform policy and practice. Leading experts from the UK and abroad will share their knowledge and direct discussions with seminar participants. This process will advance what we currently know about the topic and also identify aspects that we don't know about that require more research. It will also enable a large group of people (from research, policy and practice backgrounds) with a shared commitment to healthy ageing to establish themselves as a 'network'. The network members will continue to communicate and collaborate with each other both during and beyond the lifetime of the seminar series. Who will benefit and how: The seminar series is intended to have strong and distinctive impacts in academic, policy and user communities. This will be achieved by advancing understanding of (i)physical activity engagement in older age in ways that go beyond 'how much' and 'how often', (ii)the value of using different disciplines (i.e. subject areas) and research methods to generate knowledge about this topic. Policy contributions will be made regarding how best to promote healthy ageing, through physical activity involvement. Impact will also occur through the inclusion of older participants in the co-production of research knowledge, and in the training of early career researchers to continue championing this research area. Working closely with Core Partners (British Heart Foundation, Birmingham Public Health, Sporting Equals) will enhance the research teams understanding of the relationship between research and policy.

The issue: There are currently more people over the age of 60 than ever before. The Office of National Statistics have projected that the number of people age 60 years and over will increase by 50% in the next 25 years. These demographic changes are important because people generally become less physically active as they grow older. This can be detrimental to their health and well-being and has subsequent health and social care costs. Researchers have been investigating the relationship between physical activity and health for a long time. Consequently, much is known about which diseases can be prevented through physical activity, and how much and how often activity should be undertaken. This information is useful, but it does not negate the fact that there are still lots of older people who are inactive. Recently, leading scientists have said that if we are to encourage people to integrate health behaviours like physical activity into their everyday life, conducting research to reconfirm that physical activity is beneficial is not enough. Instead, they say that we need to know more about the different environments, which can enable or deter physical activity in older age and shape how it is experienced. This includes people's physical environments (e.g. their access and proximity to woodlands, parks etc.) and also their social and cultural environments (e.g. the impact of their ethnicity, gender, interaction with healthcare etc.). Social scientists are well qualified to investigate issues like these. Our response: Our seminar series will bring together academics from different subject areas (e.g. sociology, psychology, geography, sport and health sciences), policy makers, health and social care practitioners, physical activity and sport providers, and those working within the voluntary and statutory sectors. Each seminar will focus on a specific issue relevant to the physical, social and cultural environments that can impact upon physical activity (PA) in older age. Specifically; (i)competitive sport in later life, (ii)physical activity during lifecourse transitions, (iii)how gender impacts upon physical activity involvement - and vice versa, (iv)experiences of physical activity amongst hard to reach groups (e.g. ethnic minorities), (v)community based initiatives to promote physical activity, (vi)E-health, (vii)PA in the outdoor natural environment, (viii)the process of using research to inform policy and practice. Leading experts from the UK and abroad will share their knowledge and direct discussions with seminar participants. This process will advance what we currently know about the topic and also identify aspects that we don't know about that require more research. It will also enable a large group of people (from research, policy and practice backgrounds) with a shared commitment to healthy ageing to establish themselves as a 'network'. The network members will continue to communicate and collaborate with each other both during and beyond the lifetime of the seminar series. Who will benefit and how: The seminar series is intended to have strong and distinctive impacts in academic, policy and user communities. This will be achieved by advancing understanding of (i)physical activity engagement in older age in ways that go beyond 'how much' and 'how often', (ii)the value of using different disciplines (i.e. subject areas) and research methods to generate knowledge about this topic. Policy contributions will be made regarding how best to promote healthy ageing, through physical activity involvement. Impact will also occur through the inclusion of older participants in the co-production of research knowledge, and in the training of early career researchers to continue championing this research area. Working closely with Core Partners (British Heart Foundation, Birmingham Public Health, Sporting Equals) will enhance the research teams understanding of the relationship between research and policy.

Detrimental effects of air pollution on child health include altered function of the lungs, brain and heart and can begin during fetal development. Therefore, pregnant women have a unique position in efforts to understand and lessen the adverse effects of air pollution. Past years have seen a focus on outdoor pollution from traffic and industry but recently attention has moved to the effects of indoor air pollution. Most people spend more than 90% of their time indoors where they are exposed to pollutants from things like frying foods, wood burning stoves and to the chemicals in clothing, furniture and cleaning products. Outdoor air pollutants also accumulate in the home especially in the colder months; exposure to indoor air pollutants also occurs at work, in school and other places we visit. The little information we have about the effects of indoor air pollution exposures during pregnancy suggests that they have negative effects on the developing baby affecting birth weight and lung function; other effects have not been studied. Our studies are designed to determine how air pollution exposures of pregnant women pass to the baby to affect organ development and poor health in childhood. By sharing our findings with local and national government, business, charities and the public we will provide them with the evidence to make changes to policy and practice that will eventually reduce the ill-effects of pregnancy air pollution exposures on child health. We will study the effects of airborne materials on different biological samples collected from pregnant women at different trimesters, not pregnant women and men. These samples will include nasal samples as a source from the airways that is safe to use in pregnancy, peripheral and umbilical cord blood, placenta and sperm and we will develop a human lung model. Samples will be exposed to PM2.5, components of house dust and volatile organic compounds, such as the chemicals found in cleaning products, alone and in combination including with other airborne materials such as pollen and viruses. This will enable us to track the passage and propagation of the response to airborne materials from the maternal airways, through the circulation to the placenta and fetus. We will measure changes in gene, protein and metabolite expression to determine if the toxicological response made differs in pregnant women. To elucidate the link between these toxicological responses and fetal organ development we will study animal models in parallel to determine what effects the maternal exposures are having. We will also study pregnant women in the community to gather data about their indoor environment. This will be linked to already gathered data about the outdoor environment and to other data collected routinely about all of us such as health data to help us understand how pregnant women change their use of indoor and outdoor environments over pregnancy and what this means for birth outcomes and later health of the child. We will collect biological samples such as nasal fluid, blood, urine and placenta from women in this cohort to see if these tissues from women with natural exposures share changes in gene, protein and metabolite expression with our laboratory models. Overall, this approach will reveal pregnancy-specific toxicological responses to airborne materials that can affect the developing offspring. All participants will be from diverse backgrounds, geographical areas and socioeconomic circumstances incorporating the lowest to highest potential exposures within the UK ensuring broad applicability of our findings and revealing the effects of health inequalities. Our activities will be supported by citizen science and vigorous management structures to ensure cohesive UK-wide consortium activities. The unique insights garnered will shape guidelines and policy and provide a step change in the implementation of behaviours and interventions to truly engender long-term health benefits for children.

This application brings together two world-renowned research- and educational-focused Universities in a unique collaboration to create an interdisciplinary training approach to meet challenges in healthcare. With complementary strengths in basic physical sciences, engineering and clinical translation, close strategic and geographical links and a CDT embedded within a top-rated teaching hospital, the KCL/ICL alliance is superbly placed to train the next generation of imaging scientists and research leaders. The CDT will provide a unique interdisciplinary training program to develop the skills for creating innovative technical solutions through integration of the physical sciences, engineering and biological and clinical disciplines. The Centre will be integrated into a large research portfolio in medical imaging funded through EPSRC/Wellcome Trust Medical Engineering Centres, MRC centres, the CRUK/EPSRC Cancer Imaging Centres, and the BHF Centres of Excellence. In order to foster clinical translation of research, the CDT will be linked into two Academic Health Science Centres and NIHR-Biomedical Research Centres. The CDT will create a critical mass of teachers and researchers to establish an interdisciplinary training program by bringing together students from different disciplines to work on research topics in medical imaging. The CDT will feature a 1 + 3 years MRes+PhD structure and will manage the students as a single cohort. We have developed the different phases of the PhD programme, i.e. Recruitment, MRes, PhD and Alumni, to achieve the highest quality in training, research and career development for the individual student. We place a strong emphasis on clinical translation, therefore the CDT will continue with a formal training programme in clinical applications in parallel to the PhD projects. In addition, the teaching location of the Centre in a dedicated, newly-refurbished CDT teaching hub within a world-class teaching hospital engenders strong links with the NHS and provides further enhanced opportunities for clinical translation. The first and foremost goal of this CDT will be to provide the highest quality supervision for individual students. To achieve this, we will combine the experience of senior supervisors with the energy and development of more junior academics. At the start of the CDT, we will be defining PhD projects from 60 supervisors with world-leading research expertise in the underpinning of the multidisciplinary themes in medical imaging. All of those scientists have a track record in PhD supervision and delivering research funded by research councils. We have also identified clinical champions in three major disease areas (Cardiology, Oncology, Neuro) who will organize training in clinical application. This training is designed to forge interactions between scientists and clinicians. It will provide students with valuable contacts with whom they can discuss clinical implications of their PhD research. The CDT will provide training of a new generation of scientists with skills in interdisciplinary research, clinical translation and entrepreneurship. The focus of both graduate training and the individual student research projects will be to innovate medical imaging technologies in the care cycle of patients across a range of diseases. Another central theme within the program will be training to translate innovations into commercial products. For this, we will leverage our strong industrial links and have obtained financial commitment for more than 25 co-funded industrial CDT studentships from various industrial partners. The partners, including new UK-based SMEs and start-up companies, will also provide internships to enable career paths into industry.